Selenium is an essential trace metal which has important antioxidant functions in nutrition. The long range objectives of these studies are to understand the role of selenoprotein P in promoting neuronal survival and protecting neuronal cells from oxidative stress. This application proposes to build upon recent discoveries with regard to the novel selenoprotein and selenoprotein P. Three specific aims are proposed: (1) To investigate the function of selenoprotein P in neuronal survival and protection from oxidative stress, and mechanism of selenium uptake, storage, and utilization. These studies will use cells of neuronal origin, transfected with various constructs of selenoproteins P, to do mapping of the functional domains and identification of interaction partners of selenoprotein P, the ability to provide protection from oxidative stress, and analysis for mechanism of selenium storage, uptake and utilization. (2) The role of selenoprotein P in protection from heavy metal toxicity. Investigations will study protection from heavy metal toxicity, regulation of selenoprotein P expression by heavy metals, and co-localization of heavy metals and selenium within transfected cells. (3) Expression and function of selenoprotein P in zebra fish. In situ hybridization and determination of requirements and function of selenoprotein P in Zebra fish will be conducted.